In the process of chromatography, a mixture of chemical substances may be resolved or separated by means of their selective retardation as they are transported by a moving fluid or buffer solution through a resin packed in a chromatography column. A solution of the substances to be separated is referred to as the mobile phase of the system. The resin is known as the stationary phase and comprises finely divided particles which may be in the form of a gel slurry.
A chromatography column, referred to herein as simply a “column,” typically comprises a hollow, vertically disposed cylindrical housing including, at the upper end, a liquid dispensing section through which the mobile phase is dispensed to the porous resin. A liquid collecting section is located at the lower end of the column. The resin through which the mobile phase percolates is located between these sections.
The mobile phase is pumped or poured into the top of a chromatography column filled with the resin to which the substances to be separated can bind differentially as the mobile phase percolates down the column.
Binding of chromatography resins is known to generally increase with increasing residence time, that is, contact time with the resin in the chromatography column. In the field of bio-manufacturing, there has been a well-recognized need to choose between the loading of columns at relatively fast flow rates in order to complete steps quickly, versus the loading at a slower flow rate in order to maximize resin binding, the slower flow rate resulting in an increase in process time. Traditionally an acceptable middle ground has been chosen as a compromise option. At a given flow rate, as binding sites on the resin become occupied, resin capacity decreases because the percentage of available binding sites decreases with increased time.
Experiments relating to dual flow rate loading have been described, wherein material is loaded quickly at first; then loaded at a lower flow rate once the resin capacity is decreased. Additionally, techniques such as simulated moving bed (SMB), and simultaneous multi-column chromatography (SMCC) have been developed. These techniques seek to make better use of the resin over time by dividing the resin volume over multiple columns, each of which can be operating in a different portion of the chromatography sequence, for example, equilibration; load; wash; elution; and strip.
In the field of bio-manufacturing, recent developments in techniques of cell culture have increased productivity. However, the productivity and economics of bio-manufacturing are still limited by downstream processing, especially by the widely used technique of bind-and-elute chromatography.
Thus, a need exists for a new system for adjusting chromatographic operating parameters to process conditions, while maximizing throughput, the operating parameters including, for example, variable load rates.